Abstract
Malignant pleural mesothelioma is a rare and aggressive malignancy arising from mesothelial cells that line the serous membranes of the body. Cytotoxic chemotherapy has been a mainstay of therapy, resulting in a modest improvement in overall survival, but toxicity limits the eligible patient population. Few targeted agents beyond bevacizumab have demonstrated superior efficacy compared to placebos. With an improved understanding of the relationship between the immune system and cancer progression, immunotherapies are playing a greater role in the treatment of many cancers. Several early- and late-phase trials in malignant pleural mesothelioma, including assessments of the first-line efficacy of combination ipilimumab/nivolumab treatment, have now demonstrated promising results for both immune checkpoint inhibition and cell-based therapies. These immune therapies are likely to play a central role in the treatment of this disease going forward.
Highlights
Malignant pleural mesothelioma (MPM) is a rare but aggressive malignancy of which the incidence is highly correlated to the local importation and use of asbestos [1]
MPM is associated with a diverse immune microenvironment consisting of tumorassociated macrophages (TAMS), cancer-associated fibroblasts, T-lymphocytes, and myeloidderived suppressor cells, which contribute to MPM pathogenesis through complex autocrine and paracrine signaling, as reviewed in [8]
Monoclonal antibodies directed against cytotoxic T lymphocyte antigen 4 (CTLA4) or programmed cell death 1 (PD-1) or its cognate ligand programmed cell death ligand 1 (PD-L1) have received regulatory approval across the globe, alone or in combination with chemotherapy, for the treatment of a variety of malignancies, including other thoracic cancers such as non-small-cell lung cancer (NSCLC) and small-cell lung cancer (SCLC) [22–25]
Summary
Malignant pleural mesothelioma (MPM) is a rare but aggressive malignancy of which the incidence is highly correlated to the local importation and use of asbestos [1]. A United States Surveillance, Epidemiology and End Results (SEER) database review of 14,228 cases diagnosed from 1973–2009 revealed that 59% of patients present with distant metastatic disease and only 23% of cases were treated with a cancer-directed surgery [3]. As in many other common cancers, cytotoxic chemotherapy is the traditional standard of treatment for patients with local or advanced MPM. With the loss of immune control recognized as a “hallmark” of carcinogenesis [5] and the development of tolerable agents, immune-directed therapies are playing a greater role in the treatment of mesothelioma. The recently reported improved efficacy of a first-line combination of ipilimumab/nivolumab over standard platinum/pemetrexed treatment represents a breakthrough for immune therapies in the treatment of MPM
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
